癌症治療已成為全球討論的重要議題，基因療法在近年來掀起一陣浪潮，因此協助遞送基因的載體是全球致力研究的目標，期望能開發高生物安全性、高轉染效率的非病毒載體。多肽高分子具有良好的生物相容性、可修飾調節聚合物結構，成為基因治療的優選材料。本研究旨在合成具高生物相容性之聚胺酸，作為有效遞送基因之載體，並探討在3D 類器官培養的轉染效果。本實驗分別以三臂(3s)、六臂(6s)、十二臂(12s)、二十四臂(24s)的星狀結構作為起始劑，賴胺酸與丙胺酸作為材料，經由胺基酸N-羧酸酐(N-carboxyanhydride ring-opening polymerization, NCA-ROP)合成所需聚胺酸，透過起始劑嵌段賴胺酸作為第一鏈段，合成出星狀聚賴胺酸(s-PZLL)，再嵌上第二鏈段丙胺酸(s-PZLL-PLA)，並將每種樣品的賴胺酸保護基切除，合成出帶正電之星狀聚胺酸：3s-PLL10、3s-PLL10-b- PLA 5、6s-PLL10、6s-PLL10-b- PLA 5、12s-PLL10、12s-PLL10-b- PLA 5、24s-PLL10、24s-PLL10-b- PLA 5，藉由1H NMR、GPC分析聚合度、分子量，同時以FT-IR與CD鑑定二級結構；再透過陽離子星狀聚胺酸與負電之pDNA以靜電作用力複合，以電泳遷移試驗篩選出適當N/P ratio之範圍、TEM與DLS分析複合物粒徑與型態，透過溶血實驗與3D細胞培養之毒性測試確認星狀聚胺酸之生物安全性，最後，將陽離子星狀聚胺酸作為載體遞送到3D球形細胞，在模仿人體生理環境下，觀察綠色螢光蛋白的表達，篩選出6s-PLL10-b- PLA 5、12s-PLL10-b- PLA 5、24s-PLL10 b- PLA 5具有較高的轉染效率，考量毒性與複合物的核酸承載量，以6s-PLL10-b- PLA 5進行RNAi轉染，藉由西方墨點法進行癌細胞凋亡試驗，發現6s-PLL10- b- PLA 5確實可抑制癌細胞的生長，並誘導癌細胞凋亡，是可有效傳遞基因並抑制癌症的優良載體。

Gene therapy has been major research in medical and pharmaceutical sciences nowadays, due to the introduction of exogenous genetic material into somatic cells of patients to modulate the expression of desired proteins. The study aims to develop a series of star-shaped polypeptides with different arm as effective gene carriers without immunogenicity. 3s-PLL10, 3s-PLL10-b-PLA5, 6s-PLL10, 6s-PLL10-b-PLA5, 12s-PLL10, 12s-PLL10-b-PLA5, 24s-PLL10 and 24s-PLL10-b-PLA5 were synthesized to investigate their transfection efficacy in organoids cell model which can directly modify a bunch of genes. The star-shaped polypeptides were not only biocompatible but also able to overcome various transfection barriers. Physical property such as degree of polymerization and secondary conformation were analyzed by 1H NMR, GPC, FTIR and CD. The range of N/P ratio was determined by Gel retardation assay. Size of the complexes and zeta potential were obtained by DLS measurement. TEM images presented the morphology of the complexes which were compact and spherical.
It was expected to enhance cellular uptake in the suitable N/P ratio. Green fluorescence protein was transfected to cell at different N/P ratio. The results demonstrated that the star-shaped polypeptides which contain alanine displayed higher transfection efficacy. 6s-PLL10-b-PLA 5, 12s-PLL10-b-PLA 5 exhibited higher transfection efficiency in 3D organoid model which was an effective result to transfer RNAi to cancer cell in next step. After cancer cell was treated by 6s-PLL10-b-PLA5, cell apoptosis was observed, and the cancer gene expression was successfully inhibited. In summary, was develop as a promising gene vector with high transfection efficiency and anticancer property.

1. Bouard, D., N. Alazard‐Dany, and F.L. Cosset, Viral vectors: from virology to transgene expression. British journal of pharmacology. 157(2): p. 153-165. 2009
2. Ozturk, S., et al., Clinical and surgical aspects of medical materials’ biocompatibility, in Handbook of Biomaterials Biocompatibility. Elsevier. p. 219-250. 2020
3. Kohane, D.S. and R. Langer, Biocompatibility and drug delivery systems. Chemical Science. 1(4): p. 441-446. 2010
4. Naahidi, S., et al., Biocompatibility of hydrogel-based scaffolds for tissue engineering applications. Biotechnology advances. 35(5): p. 530-544. 2017
5. Stefanovic, S., et al., Star-shaped poly (l-lysine) with polyester bis-MPA dendritic core as potential degradable nano vectors for gene delivery. Polymer Chemistry. 14(27): p. 3151-3159. 2023
6. Mandal, H., et al., ε-Poly-l-Lysine/plasmid DNA nanoplexes for efficient gene delivery in vivo. International Journal of Pharmaceutics. 542(1-2): p. 142-152. 2018
7. Zhou, T., et al., Nanostructure-induced DNA condensation. Nanoscale. 5(18): p. 8288-8306. 2013
8. Pichon, C., C. Gonçalves, and P. Midoux, Histidine-rich peptides and polymers for nucleic acids delivery. Advanced drug delivery reviews. 53(1): p. 75-94. 2001
9. Thomas, M. and A. Klibanov, Non-viral gene therapy: polycation-mediated DNA delivery. Applied microbiology and biotechnology. 62: p. 27-34. 2003
10. Nair, A., et al., Hybrid nanoparticle system integrating tumor-derived exosomes and poly (amidoamine) dendrimers: implications for an effective gene delivery platform. Chemistry of Materials. 35(8): p. 3138-3150. 2023
11. Riley, M.K. and W. Vermerris, Recent advances in nanomaterials for gene delivery—a review. Nanomaterials. 7(5): p. 94. 2017
12. Tarvirdipour, S., et al., Peptide-based nanoassemblies in gene therapy and diagnosis: paving the way for clinical application. Molecules. 25(15): p. 3482. 2020
13. Li, W., F. Nicol, and F.C. Szoka Jr, GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Advanced drug delivery reviews. 56(7): p. 967-985. 2004
14. Stepanova, M., et al., Polypeptide-based systems: From synthesis to application in drug delivery. Pharmaceutics. 15(11): p. 2641. 2023
15. ADMINISTRATION, U.S.F.D., What is Gene Therapy? 2018
16. Xu, Y., et al., Organoids in lung cancer: A teenager with infinite growth potential. Lung Cancer. 172: p. 100-107. 2022
17. Yang, S., et al., Organoids: The current status and biomedical applications. MedComm. 4(3): p. e274. 2023
18. Wang, H., et al., Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency. The journal of gene medicine. 21(7): p. e3101. 2019
19. Wang, C., et al., Recent progress of non-linear topological structure polymers: synthesis, and gene delivery. Journal of Nanobiotechnology. 22(1): p. 40. 2024
20. Gorzkiewicz, M., et al., Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro. Bioorganic Chemistry. 95: p. 103504. 2020
21. Cavalli, S., F. Albericio, and A. Kros, Amphiphilic peptides and their cross-disciplinary role as building blocks for nanoscience. Chemical Society Reviews. 39(1): p. 241-263. 2010
22. Zheng, M., et al., Poly (α-l-lysine)-based nanomaterials for versatile biomedical applications: Current advances and perspectives. Bioactive Materials. 6(7): p. 1878-1909. 2021
23. Wibowo, S.H., et al., Polypeptide films via N-carboxyanhydride ring-opening polymerization (NCA-ROP): past, present and future. Chemical communications. 50(39): p. 4971-4988. 2014
24. Leuchs, H., Ueber die Glycin‐carbonsäure. Berichte der deutschen chemischen Gesellschaft. 39(1): p. 857-861. 1906
25. Kricheldorf, H.R., Polypeptides and 100 years of chemistry of α‐amino acid N‐carboxyanhydrides. Angewandte Chemie International Edition. 45(35): p. 5752-5784. 2006
26. Huang, J. and A. Heise, Stimuli responsive synthetic polypeptides derived from N-carboxyanhydride (NCA) polymerisation. Chemical Society Reviews. 42(17): p. 7373-7390. 2013
27. Farthing, A., 627. Synthetic polypeptides. Part I. Synthesis of oxazolid-2: 5-diones and a new reaction of glycine. Journal of the Chemical Society (Resumed). p. 3213-3217. 1950
28. Daly, W.H. and D. Poché, The preparation of N-carboxyanhydrides of α-amino acids using bis (trichloromethyl) carbonate. Tetrahedron Letters. 29(46): p. 5859-5862. 1988
29. Mazo, A.R., et al., Ring opening polymerization of α-amino acids: advances in synthesis, architecture and applications of polypeptides and their hybrids. Chemical society reviews. 49(14): p. 4737-4834. 2020
30. Zhou, X. and Z. Li, Advances and biomedical applications of polypeptide hydrogels derived from α‐amino acid N‐carboxyanhydride (NCA) polymerizations. Advanced healthcare materials. 7(15): p. 1800020. 2018
31. Byrne, M., et al., Star‐Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics. Macromolecular rapid communications. 36(21): p. 1862-1876. 2015
32. Yang, J. and G.-F. Luo, Peptide-based vectors for gene delivery. Chemistry. 5(3): p. 1696-1718. 2023
33. Sung, Y.K. and S. Kim, Recent advances in the development of gene delivery systems. Biomaterials research. 23(1): p. 8. 2019
34. Han, S.-o., et al., Development of biomaterials for gene therapy. Molecular Therapy. 2(4): p. 302-317. 2000
35. Jones, C.H., et al., Overcoming nonviral gene delivery barriers: perspective and future. Molecular pharmaceutics. 10(11): p. 4082-4098. 2013
36. Lentz, T.B., S.J. Gray, and R.J. Samulski, Viral vectors for gene delivery to the central nervous system. Neurobiology of disease. 48(2): p. 179-188. 2012
37. Mahato, M., G.R. Jayandharan, and P.K. Vemula, Viral-and non-viral-based hybrid vectors for gene therapy. Gene and Cell Therapy: Biology and Applications. p. 111-130. 2018
38. Pack, D.W., et al., Design and development of polymers for gene delivery. Nature reviews Drug discovery. 4(7): p. 581-593. 2005
39. Xiao, Y., et al., Engineering nanoparticles for targeted delivery of nucleic acid therapeutics in tumor. Molecular Therapy-Methods & Clinical Development. 12: p. 1-18. 2019
40. Yang, Z., et al., Synthetic helical polypeptide as a gene transfection enhancer. Biomacromolecules. 23(7): p. 2867-2877. 2022
41. Belmadi, N., et al., Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration. Biotechnology journal. 10(9): p. 1370-1389. 2015
42. Sharma, D., et al., A review of the tortuous path of nonviral gene delivery and recent progress. International journal of biological macromolecules. 183: p. 2055-2073. 2021
43. Nayerossadat, N., T. Maedeh, and P.A. Ali, Viral and nonviral delivery systems for gene delivery. Advanced biomedical research. 1(1): p. 27. 2012
44. Urandur, S. and M.O. Sullivan, Peptide-based vectors: A biomolecular engineering strategy for gene delivery. Annual Review of Chemical and Biomolecular Engineering. 14: p. 243-264. 2023
45. Urello, M., W.-H. Hsu, and R.J. Christie, Peptides as a material platform for gene delivery: Emerging concepts and converging technologies. Acta Biomaterialia. 117: p. 40-59. 2020
46. Felgner, P.L., et al., Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proceedings of the National Academy of Sciences. 84(21): p. 7413-7417. 1987
47. Zhang, S., et al., Cationic compounds used in lipoplexes and polyplexes for gene delivery. Journal of controlled release. 100(2): p. 165-180. 2004
48. Kwoh, D.Y., et al., Stabilization of poly-L-lysine/DNA polyplexes for in vivo gene delivery to the liver. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression. 1444(2): p. 171-190. 1999
49. Flory, P.J., Molecular size distribution in three dimensional polymers. I. Gelation1. Journal of the American Chemical Society. 63(11): p. 3083-3090. 1941
50. Shao, N., et al., Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity. International journal of nanomedicine. p. 3361-3372. 2011
51. Dufès, C., I.F. Uchegbu, and A.G. Schätzlein, Dendrimers in gene delivery. Advanced drug delivery reviews. 57(15): p. 2177-2202. 2005
52. Diebold, S.S., et al., Mannose polyethylenimine conjugates for targeted DNA delivery into dendritic cells. Journal of biological chemistry. 274(27): p. 19087-19094. 1999
53. Boussif, O., et al., A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proceedings of the National Academy of Sciences. 92(16): p. 7297-7301. 1995
54. Tang, M.X., C.T. Redemann, and F.C. Szoka, In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconjugate chemistry. 7(6): p. 703-714. 1996
55. Kaur, D., et al., A review on comparative study of PPI and PAMAM dendrimers. Journal of Nanoparticle Research. 18: p. 1-14. 2016
56. Pishavar, E., et al., Recent advances of dendrimer in targeted delivery of drugs and genes to stem cells as cellular vehicles. Biotechnology progress. 37(4): p. e3174. 2021
57. Singh, V., A. Sahebkar, and P. Kesharwani, Poly (propylene imine) dendrimer as an emerging polymeric nanocarrier for anticancer drug and gene delivery. European Polymer Journal. 158: p. 110683. 2021
58. Medina, S.H. and M.E. El-Sayed, Dendrimers as carriers for delivery of chemotherapeutic agents. Chemical reviews. 109(7): p. 3141-3157. 2009
59. Tian, H., et al., Polylysine-modified polyethylenimine inducing tumor apoptosis as an efficient gene carrier. Journal of controlled release. 172(2): p. 410-418. 2013
60. Walsh, D.P., et al., Bioinspired star-shaped poly (l-lysine) polypeptides: efficient polymeric nanocarriers for the delivery of DNA to mesenchymal stem cells. Molecular pharmaceutics. 15(5): p. 1878-1891. 2018
61. Kadlecova, Z., et al., DNA delivery with hyperbranched polylysine: A comparative study with linear and dendritic polylysine. Journal of controlled release. 169(3): p. 276-288. 2013
62. Byrne, M., et al., Molecular weight and architectural dependence of well-defined star-shaped poly (lysine) as a gene delivery vector. Biomaterials science. 1(12): p. 1223-1234. 2013
63. Luo, K., et al., Peptide dendrimers as efficient and biocompatible gene delivery vectors: Synthesis and in vitro characterization. Journal of controlled release. 155(1): p. 77-87. 2011
64. Wang, X., et al., Synthesis and evaluation of phenylalanine-modified hyperbranched poly (amido amine) s as promising gene carriers. Biomacromolecules. 11(1): p. 245-251. 2010
65. Liu, C., et al., Synthesis of Copolymers Polyethyleneimine‐co‐Polyphenylalanine as Gene and Drug Codelivery Carrier. Macromolecular Bioscience. 21(5): p. 2100033. 2021
66. Kono, K., et al., Transfection activity of polyamidoamine dendrimers having hydrophobic amino acid residues in the periphery. Bioconjugate chemistry. 16(1): p. 208-214. 2005
67. Tan, J., et al., Synthetic macromolecules as therapeutics that overcome resistance in cancer and microbial infection. Biomaterials. 252: p. 120078. 2020
68. Tan, G., et al., Amino acids functionalized dendrimers with nucleus accumulation for efficient gene delivery. International Journal of Pharmaceutics. 602: p. 120641. 2021
69. Deng, J., et al., Self-assembled cationic micelles based on PEG-PLL-PLLeu hybrid polypeptides as highly effective gene vectors. Biomacromolecules. 13(11): p. 3795-3804. 2012
70. Sato, T., et al., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 459(7244): p. 262-265. 2009
71. Scalise, M., et al., From spheroids to organoids: the next generation of model systems of human cardiac regeneration in a dish. International journal of molecular sciences. 22(24): p. 13180. 2021
72. Stewart, W.E. and T.H. Siddall, Nuclear magnetic resonance studies of amides. Chemical Reviews. 70(5): p. 517-551. 1970
73. Mlynárik, V., Introduction to nuclear magnetic resonance. Analytical Biochemistry. 529: p. 4-9. 2017
74. Callaghan, P.T., Principles of nuclear magnetic resonance microscopy. Clarendon press 1993
75. Gorbunov, A., L.Y. Solovyova, and V. Pasechnik, Fundamentals of the theory and practice of polymer gel-permeation chromatography as a method of chromatographic porosimetry. Journal of Chromatography A. 448: p. 307-332. 1988
76. Potschka, M., Universal calibration of gel permeation chromatography and determination of molecular shape in solution. Analytical biochemistry. 162(1): p. 47-64. 1987
77. Ma, J., et al., Application of gel permeation chromatography technology in asphalt materials: A review. Construction and Building Materials. 278: p. 122386. 2021
78. Khan, S.A., et al., Fourier transform infrared spectroscopy: fundamentals and application in functional groups and nanomaterials characterization. Handbook of materials characterization. p. 317-344. 2018
79. Liu., X., ORGANIC CHEMISTRY I. Kwantlen Polytechnic University 2021
80. Baker, M.J., et al., Using Fourier transform IR spectroscopy to analyze biological materials. Nature protocols. 9(8): p. 1771-1791. 2014
81. Jemison, H., et al., Application and use of the ATR, FT-IR method to asphalt aging studies. Fuel science & technology international. 10(4-6): p. 795-808. 1992
82. Sadat, A. and I.J. Joye, Peak fitting applied to fourier transform infrared and raman spectroscopic analysis of proteins. Applied Sciences. 10(17): p. 5918. 2020
83. Stani, C., et al., FTIR investigation of the secondary structure of type I collagen: New insight into the amide III band. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 229: p. 118006. 2020
84. Kaur, H., et al., Fundamentals of ATR-FTIR Spectroscopy and Its Role for Probing In-Situ Molecular-Level Interactions. Modern Techniques of Spectroscopy: Basics, Instrumentation, and Applications. p. 3-37. 2021
85. Barth, A., Infrared spectroscopy of proteins. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 1767(9): p. 1073-1101. 2007
86. Smith, B.M., L. Oswald, and S. Franzen, Single-pass attenuated total reflection Fourier transform infrared spectroscopy for the prediction of protein secondary structure. Analytical chemistry. 74(14): p. 3386-3391. 2002
87. Goormaghtigh, E., J.-M. Ruysschaert, and V. Raussens, Evaluation of the information content in infrared spectra for protein secondary structure determination. Biophysical journal. 90(8): p. 2946-2957. 2006
88. Yang, H., et al., Obtaining information about protein secondary structures in aqueous solution using Fourier transform IR spectroscopy. Nature protocols. 10(3): p. 382-396. 2015
89. Nordén, B., A. Rodger, and T. Dafforn, Linear dichroism and circular dichroism: a textbook on polarized-light spectroscopy. Royal Society of Chemistry 2019
90. Johnson Jr, W.C., Secondary structure of proteins through circular dichroism spectroscopy. Annual review of biophysics and biophysical chemistry. 17(1): p. 145-166. 1988
91. Berova, N., K. Nakanishi, and R.W. Woody, Circular dichroism: principles and applications. John Wiley & Sons 2000
92. Miles, A., R.W. Janes, and B.A. Wallace, Tools and methods for circular dichroism spectroscopy of proteins: a tutorial review. Chemical Society Reviews. 50(15): p. 8400-8413. 2021
93. Bonduelle, C., Secondary structures of synthetic polypeptide polymers. Polymer Chemistry. 9(13): p. 1517-1529. 2018
94. Piñeiro, L., M. Novo, and W. Al-Soufi, Fluorescence emission of pyrene in surfactant solutions. Advances in colloid and interface science. 215: p. 1-12. 2015
95. Kaszuba, M., et al., High-concentration zeta potential measurements using light-scattering techniques. Philosophical transactions of the royal society a: mathematical, physical and engineering sciences. 368(1927): p. 4439-4451. 2010
96. Hunter, R.J., Zeta potential in colloid science: principles and applications. Vol. 2. Academic press 2013
97. Uskoković, V., Dynamic light scattering based microelectrophoresis: main prospects and limitations. Journal of dispersion science and technology. 33(12): p. 1762-1786. 2012
98. Bhattacharjee, S., DLS and zeta potential–what they are and what they are not? Journal of controlled release. 235: p. 337-351. 2016
99. Instruments., N. Transmission Electron Microscopy. Update Date. 2024
100. Scherzer, O., The theoretical resolution limit of the electron microscope. Journal of Applied Physics. 20(1): p. 20-29. 1949
101. Egerton, R., Electron Energy-Loss Spectroscopy. Microscopy and Microanalysis. 9(S02): p. 1562-1563. 2003
102. Cai, L., et al., Comparison of cytotoxicity evaluation of anticancer drugs between real-time cell analysis and CCK-8 method. ACS omega. 4(7): p. 12036-12042. 2019
103. O'Connell, L. and D.C. Winter, Organoids: past learning and future directions. Stem cells and development. 29(5): p. 281-289. 2020
104. Grigsby, J., H. Blanch, and J. Prausnitz, Effect of secondary structure on the potential of mean force for poly-L-lysine in the α-helix and β-sheet conformations. Biophysical chemistry. 99(2): p. 107-116. 2002
105. Wang, J., et al., Strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes. Advances in Colloid and Interface Science. 302: p. 102638. 2022
106. Yin, L., N. Zheng, and J. Cheng, Highly efficient SiRNA delivery mediated by cationic helical polypeptides and polypeptide-based nanosystems. SiRNA Delivery Methods: Methods and Protocols. p. 37-47. 2016
107. Manzanares, D. and V. Ceña, Endocytosis: the nanoparticle and submicron nanocompounds gateway into the cell. Pharmaceutics. 12(4): p. 371. 2020
108. Shtykalova, S., et al., Non-Viral Carriers for Nucleic Acids Delivery: Fundamentals and Current Applications. Life. 13(4): p. 903. 2023
109. Cai, X., et al., Cationic polymers as transfection reagents for nucleic acid delivery. Pharmaceutics. 15(5): p. 1502. 2023
110. Li, Y., et al., Strategies and materials of" SMART" non-viral vectors: Overcoming the barriers for brain gene therapy. Nano Today. 35: p. 101006. 2020
111. Honary, S. and F. Zahir, Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical journal of pharmaceutical research. 12(2): p. 265-273. 2013
112. Patil, S., et al., The development of functional non-viral vectors for gene delivery. International journal of molecular sciences. 20(21): p. 5491. 2019
113. Gorzkiewicz, M., et al., Poly (lysine) dendrimers form complexes with siRNA and provide its efficient uptake by myeloid cells: model studies for therapeutic nucleic acid delivery. International Journal of Molecular Sciences. 21(9): p. 3138. 2020
114. Jeong, H., et al., In vitro blood cell viability profiling of polymers used in molecular assembly. Scientific reports. 7(1): p. 9481. 2017
115. de la Harpe, K.M., et al., The hemocompatibility of nanoparticles: a review of cell–nanoparticle interactions and hemostasis. Cells. 8(10): p. 1209. 2019
116. Kodama, Y., et al., Quaternary complexes modified from pDNA and poly-L-lysine complexes to enhance pH-buffering effect and suppress cytotoxicity. Journal of pharmaceutical sciences. 104(4): p. 1470-1477. 2015
117. Liu, X., et al., Amphipathicity determines different cytotoxic mechanisms of lysine-or arginine-rich cationic hydrophobic peptides in cancer cells. Journal of Medicinal Chemistry. 59(11): p. 5238-5247. 2016
118. Tachi, T., et al., Position-dependent hydrophobicity of the antimicrobial magainin peptide affects the mode of peptide− lipid interactions and selective toxicity. Biochemistry. 41(34): p. 10723-10731. 2002
119. Grau-Campistany, A., et al., Hydrophobic mismatch demonstrated for membranolytic peptides and their use as molecular rulers to measure bilayer thickness in native cells. Scientific Reports. 5(1): p. 9388. 2015
120. Jain, K., et al., Dendrimer toxicity: Let's meet the challenge. International journal of pharmaceutics. 394(1-2): p. 122-142. 2010
121. Zhang, R., et al., The effect of side-chain functionality and hydrophobicity on the gene delivery capabilities of cationic helical polypeptides. Biomaterials. 35(10): p. 3443-3454. 2014
122. Samal, S.K., et al., Cationic polymers and their therapeutic potential. Chemical Society Reviews. 41(21): p. 7147-7194. 2012